Full utilization of model organisms requires direct analysis of relevant tissues with histological sections. Analysis of tissues in the musculoskeletal system is technically challenging due to the nature of the tissues involved, which requires specialized techniques and anatomical knowledge to obtain the necessary sections. The creation of Core C has provided the technical and advisory resources and the operational structure to enable our research base to take full advantage of histology-based techniques, and has greatly enhanced the research programs of our investigators in the Core Center for Musculoskeletal Biology and Medicine. A large number of specific histochemical stains, as well as in situ identification of mRNA and proteins, can be employed to provide a detailed picture of developmental or pathophysiological events in our models. The overall objective of the Core is to provide histological services for the identification and analysis of molecular phenotypes of our target tissues - bone, cartilage, muscle, tendon and ligament - in an array of model organisms. Although the bulk of the work submitted by our user base comes from genetically modified mice, we also aim to facilitate histological analysis of other organisms including rat, rabbit, dog and zebrafish, as well as human samples. The services to be offered include tissue processing (paraffin, methylmethacrylate, and frozen), sectioning, and staining with an array of techniques. We also provide consultation for project planning and data analysis, and training for users in sectioning, in situ mRNA hybridization, immunohistochemistry, and quantitative histomorphometry. Finally, the Core provides the entire user base with education on appropriate methods for experimental design and data analysis related to all Core services. The strength of the Core lies in our expert staff, quality control, and close communication with investigators at all stages of their projects to ensure optimal histology-based analysis. In its first 4 years of operation, the Core has adapted to the needs of its investigator base, and this will be continued in the future as it is critical to our success. Importantly, this Core complements the specific functional analyses proposed in Core B and the new animal models generated by Core D.